SUMMARY PARAGRAPH for HSP26
HSP26 and HSP42 encode the cytosolic members of the small heat shock protein (sHSP) family of molecular chaperones (2, 9). sHSPs bind and prevent unfolded substrate proteins from irreversibly forming large protein aggregates. Bound substrate proteins can eventually be released and refolded in either a spontaneous or chaperone-assisted manner (reviewed in 10). Hsp42p functions in both unstressed and stressed cells, while Hsp26p activity is found only under stress conditions; the target substrate profiles of the two chaperones overlap by approximately 90% (11). Null mutations in hsp26 or hsp42 cause abnormal cell morphology that resembles the effects of dehydration, aging, cytoskeleton damage, or cell wall damage (11).
The HSP26 transcript is undetectable in unstressed cells but is strongly induced by heat shock, salt shock, cell cycle arrest, nitrogen starvation, carbon starvation, oxidative stress, and low pH (12, 13 and reviewed in 10). Under these conditions of stress, HSP26 expression is upregulated by the transcription factors Hsf1p and Msn2p/Msn4p which respectively bind heat shock elements and stress elements found in the HSP26 promoter (13).
Twelve Hsp26p dimers assemble to form a 24-subunit homo-oligomeric complex shaped like a hollow sphere (14, 15). Elevated temperature is required to activate this complex: heat shock causes a conformational change in Hsp26p that enables the complex to bind substrate proteins (6 and references therein). Higher temperatures also coincide with the disassociation of the complex back into dimers and it had been thought that these dimers were the active form of Hsp26p. However, it has been more recently shown that dimer reformation is not necessary for Hsp26p activation and chaperone function (14, 16).
All sHSP chaperones contain a highly conserved alpha-crystallin domain in their C-terminus, and sHSPs have been identified in archaea, plants, insects, cows, and humans (6, 1). Mutations in human sHSPs have been linked to the cardiovascular disorder desmin-related myopathy (OMIM), the neuromuscular disease Charcot-Marie-Tooth disease (OMIM), distal hereditary motor neuropathy (OMIM), and hereditary cataracts (OMIM) (15 and references therein).
Last updated: 2007-07-26